In order to investigate the effects of protein opening methods on the antigenicity and enzymatic cross-linking of whey protein， heating or cysteine treatment was used to open the molecular structure of whey protein. The modified whey protein was subjected to transglutaminase （TGase） cross-linking， and the molecular weight of the modified cross-linked product and the direct TGase cross-linked product was analyzed by polyacrylamide gel electrophoresis （SDS-PAGE）. The antigenicity of whey protein was determined by an indirect competitive enzyme-linked immunosorbent assay and the hydrophobicity of whey proteins and their modified products was determined. The experimental results showed that the intrinsic fluorescence and surface hydrophobicity of the heat-treated whey protein modified product were higher than the cysteine modified product. From the results of SDS-PAGE， it was found that the cysteine-modified whey protein were more than the cross-linked product obtained by heat modification. The results of antigenic analysis showed that the heat treatment reduced the antigen content in whey protein by about 20%， and the cysteine modification reduced the antigen content in whey protein by more than 30%. The results showed that cysteine modification could significantly reduce the antigenicity of whey protein more than heat treatment.